Interaction of genetic and environmental factors regulating the immune response to environmental antigens on mucosal surfaces is being studied. The influence of exposure to cariogenic bacteria at various ages and by various routes on amount and isotype of antibody is emphasized. The model system used is based on our published observations that inbred Harvard caries-resistant (HCR) rats differ from the Harvard caries-susceptible (HCS) rats in their immune response to cariogenic Streptococcus faecalis ND547 (S.F.). We have independently tested the environmental variables that appear to influence this difference to identify a factor regulating antibody production in the gnotobiotic HCR rat. Dental caries incidence correlates well with changes in bacterial agglutinin titer, induced by mucosal associated antigen in this model. Identification of immunoglobulin class of specific antibody should help to define the mechanism of observed differences in responses and the possible protective role of secretory antibody and the mucosal immune response. We also will look for differences in maturation of Peyeis patches in the two rat strains under various gnotobiotic environments.